PCDH11Y

Summary

PCDH11Y (protocadherin 11 Y-linked, HGNC:15813) is a protein-coding gene on chromosome Yp11.2, encoding Protocadherin-11 Y-linked (Q9BZA8). Potential calcium-dependent cell-adhesion protein.

This gene belongs to the protocadherin family, a subfamily of the cadherin superfamily. The encoded protein consists of an extracellular domain containing seven cadherin repeats, a transmembrane domain, and a cytoplasmic tail that differs from those of the classical cadherins. This gene is located on the Y chromosome in a block of X/Y homology and is very closely related to its paralog on the X chromosome. The protein is thought to play a role in cell-cell recognition during development of the central nervous system. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 83259 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 21 total — 1 pathogenic
• MANE Select transcript: NM_001395587

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15813
Approved symbol	PCDH11Y
Name	protocadherin 11 Y-linked
Location	Yp11.2
Locus type	gene with protein product
Status	Approved
Aliases	PCDHY
Ensembl gene	ENSG00000099715
Ensembl biotype	protein_coding
OMIM	400022
Entrez	83259

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000215473, ENST00000333703, ENST00000362095, ENST00000400457, ENST00000620615, ENST00000621505, ENST00000622698, ENST00000698851, ENST00000698927

RefSeq mRNA: 5 — MANE Select: NM_001395587 NM_001278619, NM_001395587, NM_032971, NM_032972, NM_032973

CCDS: CCDS14776, CCDS14777, CCDS76066, CCDS94706

Canonical transcript exons

ENST00000698851 — 6 exons

Exon	Start	End
ENSE00001322750	5737272	5742224
ENSE00001350198	5056889	5057459
ENSE00001640924	5098215	5100707
ENSE00001677522	5581775	5581798
ENSE00001803775	5501057	5501255
ENSE00003737979	5000296	5000605

Expression profiles

Bgee: expression breadth ubiquitous, 111 present calls, max score 77.82.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.5278 / max 124.8681, expressed in 134 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
201098	0.5278	134

Top tissues by expression

131 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.82	gold quality
corpus callosum	UBERON:0002336	72.77	gold quality
prefrontal cortex	UBERON:0000451	72.25	gold quality
cortical plate	UBERON:0005343	69.85	gold quality
thoracic aorta	UBERON:0001515	65.79	gold quality
Brodmann (1909) area 9	UBERON:0013540	65.00	gold quality
ascending aorta	UBERON:0001496	64.96	gold quality
frontal cortex	UBERON:0001870	64.76	gold quality
primary visual cortex	UBERON:0002436	63.32	gold quality
descending thoracic aorta	UBERON:0002345	63.01	gold quality
cerebral cortex	UBERON:0000956	60.77	gold quality
ventricular zone	UBERON:0003053	60.22	gold quality
temporal lobe	UBERON:0001871	60.14	gold quality
amygdala	UBERON:0001876	60.01	gold quality
superior frontal gyrus	UBERON:0002661	59.92	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	59.43	gold quality
hypothalamus	UBERON:0001898	59.27	gold quality
popliteal artery	UBERON:0002250	58.80	gold quality
tibial artery	UBERON:0007610	58.63	gold quality
placenta	UBERON:0001987	58.35	gold quality
anterior cingulate cortex	UBERON:0009835	57.91	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	56.09	gold quality
right coronary artery	UBERON:0001625	56.09	gold quality
ganglionic eminence	UBERON:0004023	55.84	gold quality
mucosa of transverse colon	UBERON:0004991	55.31	gold quality
colonic epithelium	UBERON:0000397	54.37	silver quality
rectum	UBERON:0001052	54.15	gold quality
Ammon’s horn	UBERON:0001954	53.95	gold quality
right frontal lobe	UBERON:0002810	53.77	gold quality
urinary bladder	UBERON:0001255	53.57	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	14.32
E-HCAD-8	no	753.36
E-MTAB-6058	no	136.95
E-ANND-3	no	0.90

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR

miRNA regulators (miRDB)

227 targeting PCDH11Y, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819

Literature-anchored findings (GeneRIF, showing 11)

• A 4.8 kb cDNA was cloned from TPA-resistance LNCaP prostate cancer cells. It is an unusual protocadherin family gene with 2 large overlapping ORFs encoding homologous polypeptides, one with and one without a signal sequence. [protocadherin-PC] (PMID:12420223)
• Findings do not support the role of PCDH11Y, or more generally of a frequent specific Y chromosome, in the susceptibility to these neuropsychiatric disorders. (PMID:16331680)
• Our findings suggest a novel mechanism for the progression of CaP involving expression of PCDH-PC. This novel protocadherin induces Wnt signaling, promotes malignant behavior and hormone-resistance of CaP cells. (PMID:16637074)
• a candidate for the evolution of hominid-specific characteristics including the sexual dimorphism of cerebral asymmetry, a putative correlate of language (PMID:16874762)
• This study provided the evidence for positive selection on Protocadherin Y gene in human lineage for schizophrenia. (PMID:18938061)
• We consider that a stronger case can be mounted for the Protocadherin11X/Y gene pair located in the hominid specific Xq21.3/Yp11.2 region of homology that was generated by a duplication from the X (PMID:19125366)
• The present article investigated the patterns of alternative splicing and expression of the PCDH11X/Y genes. (PMID:19859901)
• Our data…extended the lack of association of late-onset Alzheimer’s disease to common PCDH11Y variants. (PMID:21276771)
• PCDH11Y expression was detected in the fetal neocortex, ganglionic eminences, cerebellum, and inferior olive. In the adult brain, the cerebral cortex, hippocampal formation, and cerebellum and brain stem were immunoreactive. (PMID:22744706)
• the PCDH11X/Y gene pair determines cerebral asymmetry by initiating the right shift in Homo sapiens (PMID:23600975)
• In the present study, PCDH11Yb, but not PCDH11Ya or PCDH11Yc, was expressed in germ cells isolated from the semen of all 13 men with proven fertility. However, in several subjects from various infertility classes, there was complete absence or a significant reduction in the expression of PCDH11Yb. In conclusion, expression levels of PCDH11Yb in germ cells in the semen were correlated with the fertility status of men. (PMID:28241900)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	pcdh11	ENSDARG00000098652
mus_musculus	Pcdh11x	ENSMUSG00000034755
rattus_norvegicus	Pcdh11x	ENSRNOG00000069840

Paralogs (33): CDH1 (ENSG00000039068), CDH10 (ENSG00000040731), CDH3 (ENSG00000062038), CDH19 (ENSG00000071991), CDHR2 (ENSG00000074276), CDH17 (ENSG00000079112), CDH7 (ENSG00000081138), CDHR5 (ENSG00000099834), CDH20 (ENSG00000101542), PCDH11X (ENSG00000102290), CDH23 (ENSG00000107736), CDH9 (ENSG00000113100), CDH6 (ENSG00000113361), CDH26 (ENSG00000124215), CDHR3 (ENSG00000128536), CDH15 (ENSG00000129910), CDH24 (ENSG00000139880), CDH11 (ENSG00000140937), CDH13 (ENSG00000140945), CDH18 (ENSG00000145526), CDHR1 (ENSG00000148600), CDH22 (ENSG00000149654), CDH8 (ENSG00000150394), CDH12 (ENSG00000154162), PCDH1 (ENSG00000156453), DCHS1 (ENSG00000166341), PCDH7 (ENSG00000169851), CDH2 (ENSG00000170558), CDH4 (ENSG00000179242), CDH5 (ENSG00000179776), PCDH9 (ENSG00000184226), DCHS2 (ENSG00000197410), PCDH20 (ENSG00000280165)

Protein

Protein identifiers

Protocadherin-11 Y-linked — Q9BZA8 (reviewed: Q9BZA8)

Alternative names: Protocadherin on the Y chromosome, Protocadherin prostate cancer, Protocadherin-22

All UniProt accessions (4): Q9BZA8, A0A087WUC5, A0A8V8TMG2, A0A8V8TP37

UniProt curated annotations — full annotation on UniProt →

Function. Potential calcium-dependent cell-adhesion protein.

Subunit / interactions. Interacts with CTNNB1.

Subcellular location. Cell membrane.

Tissue specificity. Expressed strongly in fetal brain and brain (cortex, amygdala, thalamus, substantia nigra, hippocampus, caudate nucleus and corpus callosum). Expressed at low level in testis. Expressed in apoptosis-resistant cells.

Disease relevance. A chromosomal aberration involving PCDH11Y is a cause of multiple congenital abnormalities, including severe bilateral vesicoureteral reflux (VUR) with ureterovesical junction defects. Translocation t(Y;3)(p11;p12) with ROBO2.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9BZA8-1	1	yes
Q9BZA8-2	2
Q9BZA8-3	3
Q9BZA8-4	4

RefSeq proteins (5): NP_001265548, NP_001382516, NP_116753, NP_116754, NP_116755 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002126	Cadherin-like_dom	Domain
IPR013164	Cadherin_N	Domain
IPR013585	Protocadherin	Domain
IPR015919	Cadherin-like_sf	Homologous_superfamily
IPR020894	Cadherin_CS	Conserved_site
IPR050174	Protocadherin/Cadherin-CA	Family

Pfam: PF00028, PF08266, PF08374

UniProt features (28 total): domain 7, glycosylation site 6, splice variant 5, sequence variant 3, region of interest 2, topological domain 2, signal peptide 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BZA8-F1	64.62	0.25

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (6): 59, 80, 86, 376, 585, 805

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 114 (showing top): GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, GOBP_MALE_GAMETE_GENERATION, FERREIRA_EWINGS_SARCOMA_UNSTABLE_VS_STABLE_DN, GOBP_CELL_CELL_ADHESION, AACTTT_UNKNOWN, ATCATGA_MIR433, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, DBP_Q6, GOBP_POSITIVE_REGULATION_OF_WNT_SIGNALING_PATHWAY, FREAC7_01, HAMAI_APOPTOSIS_VIA_TRAIL_DN, CTAWWWATA_RSRFC4_Q2, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_DN, GOCC_MOTILE_CILIUM, GOCC_SPERM_MIDPIECE

GO Biological Process (4): cell adhesion (GO:0007155), homophilic cell-cell adhesion (GO:0007156), spermatogenesis (GO:0007283), positive regulation of Wnt signaling pathway (GO:0030177)

GO Molecular Function (2): calcium ion binding (GO:0005509), cell adhesion molecule binding (GO:0050839)

GO Cellular Component (4): plasma membrane (GO:0005886), sperm head (GO:0061827), sperm midpiece (GO:0097225), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cellular process	1
cell-cell adhesion	1
developmental process involved in reproduction	1
male gamete generation	1
positive regulation of signal transduction	1
Wnt signaling pathway	1
regulation of Wnt signaling pathway	1
metal ion binding	1
protein binding	1
membrane	1
cell periphery	1
sperm flagellum	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

4 interactions, top by confidence:

A	B	Type	Score
P		psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350

BioGRID (5): PCDH11Y (Affinity Capture-RNA), PCDH11Y (Affinity Capture-MS), PCDH11Y (Negative Genetic), PCDH11Y (Protein-peptide), PCDH11Y (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A7MB46, F8W3X3, O14917, O35902, O54800, O97799, P05622, P16234, P20786, P26618, P26619, P32926, P35546, P55286, P55289, P79749, P97291, Q05030, Q08DJ5, Q13634, Q14126, Q28889, Q5RJH3, Q68SP4, Q6KEQ9, Q6W3B0, Q6WXV7, Q6WYY1, Q6X862, Q71M42, Q7TMD7, Q7TSF0, Q7YRU7, Q80TF3, Q86SJ6, Q8AXC6, Q8AXC7, Q8BIZ0, Q8N6Y1, Q8TAB3

Diamond homologs: B8V7Q1, G5EDK5, O18926, O55075, O93319, P08641, P09803, P20310, P33146, P33147, P55289, P55291, P70407, Q00174, Q08DJ5, Q13634, Q5DRA4, Q5DRA5, Q5DRA7, Q5DRA9, Q5DWV1, Q5DWV2, Q5RJH3, Q63149, Q63315, Q6KEQ9, Q6PFX6, Q6WXV7, Q6WYY1, Q6X862, Q71M42, Q86UP0, Q8BM92, Q8QGH3, Q90762, Q90763, Q90Z37, Q91838, Q9BZA8, Q9HBT6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

21 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	4
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1048614	GRCh37/hg19 Yp11.32-11.2(chrY:10701-5080415)x2	Pathogenic

SpliceAI

3383 predictions. Top by Δscore:

Variant	Effect	Δscore
Y:5057455:TTAAG:T	donor_loss	1.0000
Y:5057456:TAAGG:T	donor_loss	1.0000
Y:5057457:AAGG:A	donor_loss	1.0000
Y:5057460:GT:G	donor_loss	1.0000
Y:5057461:T:G	donor_loss	1.0000
Y:5098204:A:AG	acceptor_gain	1.0000
Y:5098204:AT:A	acceptor_gain	1.0000
Y:5098205:T:G	acceptor_gain	1.0000
Y:5098214:GA:G	acceptor_gain	1.0000
Y:5307437:A:AG	donor_gain	1.0000
Y:5501055:A:AG	acceptor_gain	1.0000
Y:5501055:AGTCC:A	acceptor_gain	1.0000
Y:5501056:G:GA	acceptor_gain	1.0000
Y:5501056:GT:G	acceptor_gain	1.0000
Y:5501056:GTC:G	acceptor_gain	1.0000
Y:5501056:GTCCC:G	acceptor_gain	1.0000
Y:5501251:ATCTA:A	donor_gain	1.0000
Y:5501252:TCTA:T	donor_gain	1.0000
Y:5501253:CTA:C	donor_gain	1.0000
Y:5501254:TA:T	donor_gain	1.0000
Y:5501255:AG:A	donor_loss	1.0000
Y:5501256:G:GG	donor_gain	1.0000
Y:5501256:GT:G	donor_loss	1.0000
Y:5501257:T:A	donor_loss	1.0000
Y:5098199:A:AG	acceptor_gain	0.9900
Y:5098199:ATT:A	acceptor_gain	0.9900
Y:5098205:T:TA	acceptor_gain	0.9900
Y:5098212:CA:C	acceptor_loss	0.9900
Y:5098213:A:AG	acceptor_gain	0.9900
Y:5098213:A:AT	acceptor_loss	0.9900

AlphaMissense

8262 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
Y:5098341:G:C	D255H	0.999
Y:5098371:G:C	A265P	0.999
Y:5057310:G:C	D163H	0.998
Y:5057318:T:A	N165K	0.998
Y:5057318:T:G	N165K	0.998
Y:5057320:A:C	D166A	0.998
Y:5057329:C:A	P169Q	0.998
Y:5057335:T:G	F171C	0.998
Y:5098276:T:C	L233P	0.998
Y:5098372:C:A	A265D	0.998
Y:5098390:T:A	V271D	0.998
Y:5098492:C:A	A305D	0.998
Y:5098503:G:C	D309H	0.998
Y:5098654:T:A	V359D	0.998
Y:5098732:C:A	P385Q	0.998
Y:5098815:G:C	A413P	0.998
Y:5098816:C:A	A413D	0.998
Y:5098987:C:A	A470D	0.998
Y:5737325:T:A	C1136S	0.998
Y:5737326:G:C	C1136S	0.998
Y:5057254:T:A	V144D	0.997
Y:5057311:A:C	D163A	0.997
Y:5057335:T:C	F171S	0.997
Y:5057407:C:A	A195D	0.997
Y:5098405:A:C	D276A	0.997
Y:5098420:T:C	F281S	0.997
Y:5098497:G:C	D307H	0.997
Y:5098504:A:C	D309A	0.997
Y:5098504:A:T	D309V	0.997
Y:5098573:T:C	F332S	0.997

dbSNP variants (sampled 300 via entrez): RS1000297456 (Y:5219368 C>A), RS1002232889 (Y:5012189 C>A), RS1002346118 (Y:5708355 C>T), RS1003055389 (Y:5393721 C>A), RS1003261694 (Y:5593444 G>A), RS1003330852 (Y:5406294 C>A), RS1003798600 (Y:5559457 C>T), RS1004062840 (Y:5624398 C>T), RS1004437522 (Y:5594865 G>T), RS1006421155 (Y:5470063 G>T), RS1007062496 (Y:5115728 A>C), RS1007093539 (Y:5167924 G>T), RS1007396154 (Y:5311403 A>T), RS1007427331 (Y:5343272 G>T), RS1008910908 (Y:5666970 A>G)

Disease associations

OMIM: gene MIM:400022 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001613_10	Antineutrophil cytoplasmic antibody-associated vasculitis	4.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, decreases methylation, increases expression	3
Benzo(a)pyrene	decreases methylation, increases expression, increases methylation, affects methylation	2
potassium perchlorate	decreases expression	1
trichostatin A	increases expression	1
butyraldehyde	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
belinostat	affects cotreatment, increases expression	1
quinocetone	increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
Acetaminophen	increases expression	1
Lipopolysaccharides	affects cotreatment, increases expression	1
Rotenone	decreases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.